Uncovering the viral aetiology of undiagnosed acute febrile illness in Uganda using metagenomic sequencing

Shirin Ashraf, Hanna Jerome, Daniel Lule Bugembe, Deogratius Ssemwanga, Timothy Byaruhanga, John Timothy Kayiwa, Robert Downing, Jesus F. Salazar-Gonzalez, Maria G. Salazar, James G. Shepherd, Craig Wilkie, Chris Davis, Nicola Logan, Sreenu B. Vattipally, Gavin S. Wilkie, Ana Silva Filipe, Alfred Ssekagiri, Prossy Namuwulya, Henry Bukenya, Brian K. Kigozi, Weronika Witkowska McConnell, Brian J. Willett, Stephen Balinandi, Julius Lutwama, Pontiano Kaleebu, Josephine Bwogi () and Emma C. Thomson ()
Additional contact information
Shirin Ashraf: (CVR)
Hanna Jerome: (CVR)
Daniel Lule Bugembe: (UVRI)
Deogratius Ssemwanga: (UVRI)
Timothy Byaruhanga: (UVRI)
John Timothy Kayiwa: (UVRI)
Robert Downing: (UVRI)
Jesus F. Salazar-Gonzalez: (MRC-UVRI)
Maria G. Salazar: (MRC-UVRI)
James G. Shepherd: (CVR)
Craig Wilkie: University of Glasgow
Chris Davis: (CVR)
Nicola Logan: (CVR)
Sreenu B. Vattipally: (CVR)
Gavin S. Wilkie: (CVR)
Ana Silva Filipe: (CVR)
Alfred Ssekagiri: (CVR)
Prossy Namuwulya: (CVR)
Henry Bukenya: (UVRI)
Brian K. Kigozi: (UVRI)
Weronika Witkowska McConnell: (CVR)
Brian J. Willett: (CVR)
Stephen Balinandi: (UVRI)
Julius Lutwama: (UVRI)
Pontiano Kaleebu: (UVRI)
Josephine Bwogi: (UVRI)
Emma C. Thomson: (CVR)

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Viruses associated with acute febrile illness in Africa cause a spectrum of clinical disease from mild to life-threatening. Routine diagnostic methods are insufficient to identify all viral pathogens in this region. In this study, 1281 febrile Ugandan patients were prospectively recruited as part of the CDC-UVRI Acute Febrile Illness Study and pre-screened for common pathogens. 210/1281 undiagnosed samples, and 20 additional samples from viral outbreaks were subjected to metagenomic sequencing. Viral pathogens were identified in 44/230 (19%), including respiratory, hepatitis, blood-borne, gastrointestinal and vector-borne viruses. Importantly, one case of Crimean-Congo haemorrhagic fever and two cases each of Rift Valley fever, dengue and yellow fever were detected in 7/230 (3%) of cases. Le Dantec virus, last reported in 1969, was also identified in one patient. The presence of high-consequence and (re-)emerging viruses of public health concern highlights the need for enhanced population-based diagnostic surveillance in the African region.

Date: 2025
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DOI: 10.1038/s41467-025-57696-8

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